We will study olfactory deficits in early AD using functional MRI (fMRI) and quantitative volumetric MRI (vMRI). Olfactory deficits are prevalent in AD patients and can be detected in the early stages of AD. This well established finding provides a unique opportunity for us to examine the direct relationship between pathological changes in the site of early degeneration and the associated functional deficit. Studying such a relationship has been difficult and confounded with neurocognitive variables. Our long-term objective is to understand the olfactory deficits occurring in the early AD and develop reliable diagnostic tools for the early detection, monitoring and understanding the functional-pathological processes of AD. The study is designed in response to NIH PA-04-158, Ancillary Studies to the AD Neuroimaging Initiative (ADNI). The subjects will be recruited and screened with the same criteria of ADNI. The morphological data for vMRI will be acquired following ADNI standardized protocols. This design will allow the neurocognitive, biological (blood and urine) and brain morphological data acquired by this project to be added into the ADNI overall cohort. Ancillary to ADNI, we will determine how the local atrophy in the primary olfactory cortex, entorhinal and hippocampus relates to the olfactory fMRI activation in the same structures and how these sets of measurement relate to the AD psychophysical and clinical expressions. The developed neurofunctional imaging methodology in this project may be utilized for a broader study within the framework of ADNI. This project is driven by two hypotheses: 1) the olfactory deficits in early AD can be identified by olfactory fMRI; 2) olfactory fMRI activation in the primary olfactory cortex (POC) and entorhinal/hippocampal regions correlates with the degree of atrophy in these regions in MCI and AD. Aim 1: Develop, validate and standardize olfactory fMRI data acquisition methods, and the corresponding data analysis methods on the POC, entorhinal cortex and hippocampus. Aim 2: Characterize olfactory fMRI signal and its relationships with odor threshold and concentration in young and old normal controls (NC), and the changes in fMRI activation and perception of odor concentration in mild cognitive impairment (MCI) and early AD subjects. Aim 3: Identify and quantify the relationship between atrophy and olfactory dysfunction at the sites of early degeneration. [unreadable] [unreadable] [unreadable]